| INTRODUCTION Asthma is a chronic airway inflammatory disease .whose mechanism is very complex involved many kinds of inflammatory cell, medium and cytokines . Glucocorticoids(GCs) is the most effective drug in asthma therapy. But some patients are not sensitive to GCs called steroid-resistance asthma(SRA), which need high dose of GCs, some need GCs for a long time called glucocorticoid-dependent asthma, which would be worse without GCs. Treatment of GCs for long term and high dose have been associated with serious side effect at the same time. In order to avoiding the side effect of GCs, people try to replace the GCs with other acti-inflammatory drugs. With the recognition of important role of T lymphocytes in mechanism of asthma, immunosuppressant is used to cure the steroid-resistance asthma. Cyclosporin A is a lipophilic cyclic polypeptide which produces calcium-dependent, specific, reversible inhibition of transcription of interleukin-2 and several other cytokines,most notably in T helper lymphocytes. This reduces the production of a range of cytokines, inhibiting the activation and/or maturation of various cell types, including those involved in cell-mediated immunity. Oral cyclosporin A is an effective therapy in severe, corticosteroid-dependent asthma, but long term treatment would also bring many potentially serious side effects. The widely used asthma therapy agents such as p receptor agonist,GCs have partial administration method (inhaled), which can improve the concentration of drugs in the lung tissue and get effective therapy with less side effects. Neither the effect nor the mechanism of inhalation of CsA on asthma remains unclear. AIM The objectives of the present study were as follows: (1) Whether inhaled CsA effect on the allergen-induced asthma in rats; (2) Primary study on mechanism of inhaled CsA,METHOD Sprague-Dawley rats weighting 180?0g were used. They were actively sensitized with ovalbumin and two weeks later were administrated with drugs. CsA (0.5%,1%,2% , once per day) and sodium cromoglycate (SCG ,2% , once per day) were inhaled by jet nebulizer, dexamethasone (DXM, 0.5mg.籯g-1, once per day) was intraperitoneal injection(i.p.) for 7 days. On the 6th and 7th day, the animals were treated with the drugs 1 hour prior to exposure to nebulized ovalbumin (1%) 30 minutes. 24 h later , one set of the rats were anesthesized with 25% urethane 4ml/kg by i.p . Peripheral blood was obtained by the animal's tail vein, stained with Wright-Giemsa after the smear dried, and then count the different sorts of leukocyte. Right lung was lavaged with 4ml PBS, count the total number of leucocyte in bronchoalveolar lavage fluid (BALF) before centrifuged (150g for 10 min at 4 癈). Smear sedimetation of the cell before stained with Wright-Giemsa, count differential leukocyte munber. Makethe pathological section with the left lung which was fixed by 10% formalin , investigate the change of inflammation in lung tissue and do semi-quantitative analysis after stained with hematoxylin-eosin. Another set of the rats were measured the tidal volume > air flow and transpulmonary pressure after inhaling methacholine(Mch) at diffident concentration ( 0.01%^ 0.1%, 0.25%> 0.5%> 1.0%) .analysis the effect of various drugs on the reactivity to Mch.All data were analyzed statistically by Sigma Stat using One Way ANOVA and Dunnett's test. RESULT(1)The effects of various drugs on the total leucocyte and differential leucocyte in BALFCompared with normal animals (ZCS) , BALF from model group (MD) rats contained an average of 451x106 cells per liter, which was 4.5 times as much as those of ZCS group, significantly increased (P<0.01) ,and the average percentage of eosinophil increased from 0.2 + 0.4 to 34.3 + 18.8 (PO.01). Although there is no statistical difference between the model group and the group which inhaled CsA, the decrease tendency of total white cells was found, this tendency became more clearly with the dose enhanced. The percentage of the eosinophil of CsA-inhaled group was significantly...
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